PROJECT SUMMARY Epilepsy is the world?s most prominent serious brain disorder, affecting nearly 50 million people worldwide. For an estimated 30% of these patients, seizures remain poorly controlled despite maximal medical management, with significant financial costs and effects on health and quality of life. To advance the therapeutic management of epilepsy requires a more detailed understanding of the spatiotemporal dynamics that drive seizures. Characterizing these dynamics is especially difficult because, like many brain functions, the processes span spatial and temporal scales, from the fast activity of small neural populations to the slow evolution from seizure onset to termination of large brain regions. How brain signals at one scale relate to those at other scales is a significant and poorly understood issue. While animal models of epilepsy provide powerful techniques to investigate detailed neural activity within and between spatial scales, the relationship of these models to human epilepsy is unclear. An alternative to animal models of epilepsy is to study spontaneously occurring seizures in vivo from a population of human patients. However, typical in vivo clinical recordings provide only a limited view of a seizure?s multiscale dynamics. In this project, an interdisciplinary research group consisting of epileptologists and clinical neurophysiologists, a statistician, and a mathematician will study the spatiotemporal dynamics of human seizures. To do so, the team will analyze simultaneous microelectrode and macroelectrode recordings from human patients during seizures, with a particular focus on the organized spatiotemporal patterns and high frequency oscillations common in epilepsy. To make sense of these data, the team will develop and apply new methods to characterize these patterns, and link these activities to candidate mechanisms in computational models. Completion of the proposed research will represent significant progress towards a deeper understanding of human seizures, new methods to analyze and model the spatiotemporal dynamics of seizures observed in complex multiscale data, new methods to estimate model parameters and variables from brain voltage recordings, and new candidate targets for surgical treatment of epilepsy.